Trace amounts of sporadically reappearing HCV RNA can cause infection
Naga Suresh Veerapu, Su-Hyung Park, Damien C. Tully, Todd M. Allen, Barbara Rehermann
Naga Suresh Veerapu, Su-Hyung Park, Damien C. Tully, Todd M. Allen, Barbara Rehermann
View: Text | PDF
Research Article Virology

Trace amounts of sporadically reappearing HCV RNA can cause infection

Abstract

Successful hepatitis C virus (HCV) treatment is defined as the absence of viremia 6 months after therapy cessation. We previously reported that trace amounts of HCV RNA, below the sensitivity of the standard clinical assay, can reappear sporadically in treatment responders. Here, we assessed the infectivity of this RNA and infused 3 chimpanzees sequentially at 9-week intervals with plasma or PBMCs from patients who tested positive for trace amounts of HCV RNA more than 6 months after completing pegylated IFN-α/ribavirin therapy. A fourth chimpanzee received HCV RNA–negative plasma and PBMCs from healthy blood donors. The 3 experimental chimpanzees, but not the control chimpanzee, generated HCV-specific T cell responses against nonstructural and structural HCV sequences 6–10 weeks after the first infusion of patient plasma and during subsequent infusions. In 1 chimpanzee, T cell responses declined, and this animal developed high-level viremia at week 27. Deep sequencing of HCV demonstrated transmission of a minor HCV variant from the first infusion donor that persisted in the chimpanzee for more than 6 months despite undetectable systemic viremia. Collectively, these results demonstrate that trace amounts of HCV RNA, which appear sporadically in successfully treated patients, can be infectious; furthermore, transmission can be masked in the recipient by an extended eclipse phase prior to establishing high-level viremia.

Authors

Naga Suresh Veerapu, Su-Hyung Park, Damien C. Tully, Todd M. Allen, Barbara Rehermann

×

Figure 6

Specificity of CD4+ and CD8+ T cell responses.

Options: View larger image (or click on image) Download as PowerPoint
Specificity of CD4+ and CD8+ T cell responses. (A) PBMCs were obtained f...
(A) PBMCs were obtained from chimpanzee A3A017 at the indicated time points and tested in an ex vivo IFN-γ ELISPOT assay with 7 pools of HCV NS3 peptides. Each pool contained 14 overlapping 18-mer peptides of the HCV NS3 sequences of genotypes 1a, 2b, and 3 (42 peptides per pool). gt, genotype of the HCV inoculum. Mean ± SEM. (B) CD4+ and CD8+ T cells were isolated from PBMCs by magnetic cell separation and assessed for their specificity in IFN-γ ELISPOT assays using 18 pools of overlapping HCV genotype 1a peptides. Bars indicate the sum of the specific response to HCV structural and nonstructural antigens.